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    Association between polymorphisms in genes encoding estrogen receptors (ESR1 and ESR2) and excreted bisphenol A levels after orthodontic bracket bonding: a preliminary study

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    Abstract\ud \ud Background\ud Bisphenol A (BPA) is released from orthodontic composites used for bracket bonding. Genetic variations could modify the metabolism of this chemical within the organism. Considering that free BPA binds to estrogen receptors causing harmful effects to health, the present in vivo study aimed to evaluate the association between genetic polymorphisms in genes encoding estrogen receptors (ESR1 and ESR2) and excreted BPA levels in orthodontic patients.\ud \ud \ud Methods\ud Quantification of BPA levels in the urine of 16 patients was performed in a gas chromatograph mass spectrometer before (T0), at 24 h (T1), and 1 week (T2) after bracket bonding. DNA was extracted from saliva, and one genetic polymorphism in ESR1 (rs2234693) and two in ESR2 (rs4986938 and rs1256049) were analyzed by real-time PCR. Increases in BPA levels in the urine at T1 and T2 were grouped according to the genotype, and mean differences were compared by unpaired T test or Mann-Whitney test according to the normality of the data. The established alpha was 5%.\ud \ud \ud Results\ud BPA levels increased significantly at T1 and T2. There were no statistically significant differences in the increases in BPA levels according to the genotype for any genetic polymorphism (P > 0.05), at neither 24 h nor 1 week after bracket bonding.\ud \ud \ud Conclusions\ud The results suggested that there are no association between excreted BPA levels after bracket bonding and the evaluated genetic polymorphisms in ESR1 and ESR2. Further research should be performed in order to confirm these results.This work was supported by the São Paulo Research Foundation (FAPESP)\ud (funding number: 2015/06866-5) and individual fellowships from FAPESP\ud (ECK (2016/08149-1) and CAPES (KCH and GAM)

    Enzyme-linked immunosorbent assay using recombinant envelope protein 2 antigen for diagnosis of Chikungunya virus

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    Abstract Background Chikungunya (CHIKV) virus is an important mosquito-borne virus causing outbreaks of acute febrile illness with arthropathy. The detection of specific antibodies against CHIKV is used for diagnosis after the acute viremic phase of the disease. However, a major challenge for serologic diagnosis of CHIKV and other alphaviruses is the cross-reactivity of antibodies to common antigens among these viruses. In the present study, we have developed an enzyme-linked immunosorbend assay using a recombinant envelope protein 2 of CHIKV produced in Escherichia coli system, as a capture antigen. Results High titers (1600 to 12,800) of anti-CHIKV antibodies were detected in human sera analyzed by the CHIKV assay, suggesting it may detect low levels of the antibodies presence. On the other side, cross-reactivity was not observed in mouse hyperimmune sera to Mayaro virus and other alphaviruses analyzed by the CHIKV immunosorbend assay, suggesting it is a CHIKV-specific test. Fifty-nine human serum samples of CHIKV infection suspected cases were tested for immunoglobulin G (IgG) and M (IgM) antibodies detection using the CHIKV immunosorbend assay. A total of 44% (26/59) of samples were positive for IgG to CHIKV, determining 89.66% sensitivity and 100% specificity when the assay is compared to a CHIKV-specific neutralization assay. In addition, 40.6% (24/59) of samples were positive for IgM, determining 92.48% sensitivity and 79.04% specificity by a Bayesian method in the absence of a gold standard. Moreover, CHIKV immunosorbend assay showed similar sensibilities to a commercial immunochromatography assay (Lumiquick, USA) for CHIKV IgG and IgM detection. Conclusion In short, we have developed a rapid, simple, specific and sensitive CHIKV immunosorbend assay for IgG and IgM detection and our results showed potential applicability on the diagnosis of infections by this virus

    Correction to: Malaria and other febrile diseases among travellers: the experience of a reference centre located outside the Brazilian Amazon Region

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    Following publication of the original article [1], one of the authors flagged that unfortunately their last name, Doltario, was incorrectly spelled as ‘Dotrário’.This work was supported by the Grant # 2014/05337-6, São Paulo Research Foundation (FAPESP)

    Relevance of serum angiogenic cytokines in adult patients with dermatomyositis

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    Abstract Background Until now, there are few studies evaluating serum levels of angiogenic cytokines in dermatomyositis (DM). Therefore, the aims of the present study were: (a) to analyze systematically and simultaneously serum levels of angiogenin (ANG), angiopoietin (ANGPT)-1, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-1 and − 2, platelet derived growth factor (PDGF)-AA and -BB in DM; (b) to correlate the serum level of these cytokines with the DM clinical and laboratory features. Methods This is a cross sectional study, in which 48 patients with DM aged 18 to 45 years were gender-, age- and ethnicity-matched with 48 healthy individuals (control group). The serum levels of cytokines analyses were performed by multiplex immunoassay. The parameters of DM activity were based on the scores established by the International Myositis Assessment & Clinical Studies Group. Results The mean ages, gender frequencies and ethnicities were comparable between the patients with DM and the control group. A significantly higher serum FGF-1 and FGF-2 levels (P < 0.001 and P < 0.001, respectively), lower VEGF and PDGF-AA levels (P = 0.009 and P = 0.022), and comparable ANG, ANGPT-1 and PDGF-BB levels were observed in DM patients compared to controls. There was a tendency for cytokines (with the exceptions of VEGF and PDGF-BB) to correlate positively with the DM activity parameters, whereas FGF-2 correlated inversely. Moreover, FGF-1 strongly correlated with DM cutaneous manifestations. Conclusions The present data provide the relevance of different serum angiogenic cytokines in patients with DM. Additional studies will be needed to validate the data obtained in this work

    Progressive mobility program and technology to increase the level of physical activity and its benefits in respiratory, muscular system, and functionality of ICU patients: study protocol for a randomized controlled trial

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    Abstract\ud \ud Background\ud Enhanced mobility in the Intensive Care Unit (ICU) could minimize the negative effects of critical illness, such as declines in cognitive, muscular, respiratory, and functional capacity. We aim to compare the functional status at ICU discharge of patients who underwent a progressive mobilization protocol versus patients who received conventional physiotherapy. We also examine the level of physical activity in the ICU, the degree of pulmonary and muscle function, and the length of stay to analyze correlations between these variables.\ud \ud \ud Methods\ud This is a protocol for a randomized controlled trial with blind evaluation. Ninety-six ICU patients will be recruited from a single center and randomly assigned to a control group or an intervention group. To determine the level of protocol activity the patient will receive, the patients’ ability to participate actively and their muscle strength will be considered. The protocol consists of five phases, ranging from passive therapies to walking and climbing stairs. The primary outcome will be the functional status at ICU discharge, measured with the Barthel Index and the ICU Mobility Scale (IMS). Measured secondary outcomes will include the level of physical activity, maximal inspiratory and expiratory pressures, forced expiratory volume in 1 second, maximum voluntary ventilation, handgrip strength, surface electromyography of the lower limb muscles, and results of the Timed Up and Go and 2-Minute Walk tests. Evaluations will be made within 2 days of ICU discharge except for the level of activity, which will be evaluated daily. Physiological variables and activity level will be analyzed by chi-square and t tests, according to the intention-to-treat paradigm.\ud \ud \ud Discussion\ud Mobility and exercise in the ICU should be undertaken with intensity, quantity, duration, and frequency adjusted according to the patients’ status. The results of this study may contribute to new knowledge of early mobility in the ICU, activity level, and varying benefits in critical patients, directing new approaches to physiotherapeutic interventions in these patients.\ud \ud \ud Trial registration\ud Recruitment will begin in February 2017, and the expected completion date is August 2018. Patients are already being recruited.\ud ClinicalTrials.gov, ID: \ud NCT02889146\ud \ud . Registered on 3 March 2016.Funded by FAPESP Brazil 2015/18768-

    Wien effect of Cd/Zn on soil clay fraction and their interaction

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    Abstract\ud \ud Background\ud The coexistence of Cd2+ and Zn2+ ions in nature has a significant influence on their environmental behaviors in soils and bioavailability for plants. While many studies have been done on the mutual toxicity of Cd2+ and Zn2+, few studies can be found in the literature focused on the interaction of Cd2+ and Zn2+ on soil clay fractions especially in terms of energy relationship.\ud \ud \ud Results\ud The binding energies of Cd2+ on boggy soil (Histosols) particles and Zn2+ on yellow brown soil (Haplic Luvisols) particles were the highest, while those of Cd2+ and Zn2+ on paddy soil (Inceptisols) particles were the lowest. These results indicated that Cd2+ and Zn2+ have a strong capacity to adsorb in the solid phase at the soil–water interface of boggy soil and yellow brown soil, respectively. However, both Cd2+ and Zn2+ adsorbed on paddy soil particles easily release into the solution of the soil suspension. Unlike the binding energy, the higher adsorption energies of ions in boggy and yellow brown soils showed a weak binding force of ions in boggy soil and yellow brown soil. A 1:1 ratio of Cd2+ to Zn2+ promotes the mutual inhibition of their retentions. Cd2+ and Zn2+ have high mobility and bioavailability in paddy soil and yellow drab soil (Ustalfs), whereas they have high potential mobility and bioavailability in boggy soil and yellow brown soil.\ud \ud \ud Conclusion\ud In the combined system, Zn2+ had preferential adsorption than Cd2+ on soil clay fractions. Boggy soil and yellow brown soil have a low environmental risk with lower mobility and bioavailability of Cd2+ and Zn2+ while paddy soil and yellow drab soil present a substantial environmental risk. In the combined system, Cd2+ and Zn2+ restrain each other, resulting in the weaker binding force between ions and soil particles at a 1:1 ratio of Cd2+–Zn2+.This work was supported by the National Natural Science Foundation of China (Project No. 41422105) to YJW and the Natural Science Foundation of Jiangsu Province (Project No. BK20130050) to YJW and the Knowledge Innovation Program of the Chinese Academy of Sciences (ISSASIP1612) to YJW

    The power-Cauchy negative-binomial: properties and regression

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    Abstract\ud We propose and study a new compounded model to extend the half-Cauchy and power-Cauchy distributions, which offers more flexibility in modeling lifetime data. The proposed model is analytically tractable and can be used effectively to analyze censored and uncensored data sets. Its density function can have various shapes such as reversed-J and right-skewed. It can accommodate different hazard shapes such as decreasing, upside-down bathtub and decreasing-increasing-decreasing. Some mathematical properties of the new distribution can be determined from a linear combination for its density function such as ordinary and incomplete moments. The performance of the maximum likelihood method to estimate the model parameters is investigated by a simulation study. Further, we introduce the new log-power-Cauchy negative-binomial regression model for censored data, which includes as sub-models some widely known regression models that can be applied to censored data. Four real life data sets, of which one is censored, have been analyzed and the new models provide adequate fits

    Ecology, feeding and natural infection by Leishmania spp. of phlebotomine sand flies in an area of high incidence of American tegumentary leishmaniasis in the municipality of Rio Branco, Acre, Brazil

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    Abstract\ud \ud Background\ud Phlebotomine sand flies (Diptera: Psychodidae) are insects of medical importance due to their involvement in the zoonotic transmission of Leishmania spp. to vertebrates. The aim of this work was to study the ecology of the sand fly fauna of two types of environments, a rural environment (the Transacreana Road) and an urban park (Horto Florestal Park), both located in the municipality of Rio Branco in the state of Acre, Brazil. Additionally, this study intended to investigate Leishmania infection and blood meal sources of these sand flies using molecular techniques.\ud \ud \ud Methods\ud The sand fly fauna was studied in different environments (i.e. forest and peridomestic environments in a rural area, and an urban forest) using Shannon traps and HP light traps to collect sand fly specimens over 13 consecutive months (December 2014 to January 2016). For investigating natural infection by Leishmania and the source of sand fly blood meals, DNA samples were extracted from female sand flies and subjected to polymerase chain reaction targeting ITS1 and cytb genes. DNA sequencing was subsequently used to identify species of Leishmania and the source of blood meals.\ud \ud \ud Results\ud A total of 2515 individual sand flies of 43 species were collected and identified, Trichophoromyia auraensis (839; 33.35%), Trichophoromyia spp. (537; 21.35%) and Evandromyia saulensis (187; 7.43%) were more abundant in the rural area (S = 41 species) than in the urban forest. No significant differences were found in species richness between forest and peridomestic environments in the rural area (H = 0.04; P > 0.05), but a larger number of species was found in the forest. Leishmania DNA was sequenced in 13 samples, confirming the presence of L. (V.) braziliensis in Th. auraensis (n = 1), Ev. saulensis (n = 2), Ev. walkeri (n = 1), Ps. llanosmartinsi (n = 1), Pi. nevesi (n = 2), Ps. davisi (n = 1), Ps. ayrozai (n = 1), Pa. aragaoi (n = 1), Ny. antunesi (n = 1) and Ev. infraspinosa (n = 1). Only Ps. ayrozai possessed a sequence similar to that of L. (V.) guyanensis (99%). Through microscopic analysis, five specimens of Ev. saulensis were found to possess flagellate forms in the hindgut, with an infection rate of 2.4%. Samples from 33 fed females were submitted to cytb gene amplification, for which sequencing determined that all were similar to the sequence deposited on GenBank for Gallus gallus (domestic chicken).\ud \ud \ud Conclusions\ud The high abundance of Trichophoromyia auraensis and Ev. saulensis, and the detection of L. (V.) braziliensis DNA, suggests that both species may be vectors of American tegumentary leishmaniasis. Psychodopygus ayrozai was found to be infected by L. (V) braziliesnsis and L. (V.) guyanensis, and although collected in low abundance, it may be a potential vector in the region. The sand fly fauna was found to be rich and diverse with predominance of the genus Psychodopygus. Identification of food sources of fed females showed that 100% amplified a gene region compatible with the domestic chicken, which although considered refractory in the disease transmission cycle, may have an influence on the population dynamics of sand flies.This study was supported by the Fundação de Amparo à Pesquisa do Estado\ud do Acre (FAPAC) (grant agreement number PPSUS n°00011878); the\ud Foundation for Scientific and Technological Development (FIOTEC), which\ud provided the scholarship granted to Ávila MM; and Conselho Nacional de\ud Pesquisas (CNPq)

    Hypertension, mitral valve disease, atrial fibrillation and low education level predict delirium and worst outcome after cardiac surgery in older adults

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    Abstract\ud \ud Background\ud Delirium is a common complication after cardiac surgery in older adult patients. However, risk factors and the influence of delirium on patient outcomes are not well established. We aimed to determine the incidence, predisposing and triggering factors of delirium following cardiac surgery.\ud \ud \ud Methods\ud One hundred seventy-three consecutive patients aged ≥60 years were studied. Patients’ characteristics and two cognitive function assessment tests were recorded preoperatively. Perioperative variables were blood transfusion, orotracheal intubation time (OIT), renal dysfunction, and hypoxemia. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit. The composite outcome consisted of death, infection, and perioperative myocardial infarction until hospital discharge or 30 days after surgery, and for up to 18 months.\ud \ud \ud Results\ud One hundred six patients (61.27%) were men and the age was 69.5 ± 5.8 years. EuroSCORE II index was 4.06 ± 3.86. Hypertension was present in 75.14%, diabetes in 39.88%, and 30.06% were illiterate. Delirium occurred in 59 patients (34.1%). Education level (OR 0.81, 0.71–0.92), hypertension (OR 2.73, 1.16–6.40), and mitral valve disease (OR 2.93, 1.32–6.50) were independent predisposing factors for delirium, and atrial fibrillation after surgery (OR 2.49, 1.20–5.20) represented the potential triggering factor. Delirium (OR 2.35, 1.20–4.58) and OIT ≥ 900 min (OR 2.50; 1.30–4.80) were independently associated with the composite outcome.\ud \ud \ud Conclusions\ud In older adult patients submitted to cardiac surgery, delirium is a frequent complication that is associated with worst outcome. Independent risk factors for delirium included education level, hypertension, mitral valve disease, and atrial fibrillation after cardiac surgery.The present study was partially granted by Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq, Coordenação de aperfeiçoamento de pessoal de nível superior – CAPES, and Fundação Universidade Estadual do Ceará FUNECE

    The global maternal sepsis study and awareness campaign (GLOSS): study protocol

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    Abstract\ud \ud Background\ud Maternal sepsis is the underlying cause of 11% of all maternal deaths and a significant contributor to many deaths attributed to other underlying conditions. The effective prevention, early identification and adequate management of maternal and neonatal infections and sepsis can contribute to reducing the burden of infection as an underlying and contributing cause of morbidity and mortality. The objectives of the Global Maternal Sepsis Study (GLOSS) include: the development and validation of identification criteria for possible severe maternal infection and maternal sepsis; assessment of the frequency of use of a core set of practices recommended for prevention, early identification and management of maternal sepsis; further understanding of mother-to-child transmission of bacterial infection; assessment of the level of awareness about maternal and neonatal sepsis among health care providers; and establishment of a network of health care facilities to implement quality improvement strategies for better identification and management of maternal and early neonatal sepsis.\ud \ud \ud Methods\ud This is a facility-based, prospective, one-week inception cohort study. This study will be implemented in health care facilities located in pre-specified geographical areas of participating countries across the WHO regions of Africa, Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific. During a seven-day period, all women admitted to or already hospitalised in participating facilities with suspected or confirmed infection during any stage of pregnancy through the 42nd day after abortion or childbirth will be included in the study. Included women will be followed during their stay in the facilities until hospital discharge, death or transfer to another health facility. The maximum intra-hospital follow-up period will be 42 days.\ud \ud \ud Discussion\ud GLOSS will provide a set of actionable criteria for identification of women with possible severe maternal infection and maternal sepsis. This study will provide data on the frequency of maternal sepsis and uptake of effective diagnostic and therapeutic interventions in obstetrics in different hospitals and countries. We will also be able to explore links between interventions and maternal and perinatal outcomes and identify priority areas for action.This study was funded by UNDP/UNFPA/UNICEF/WHO/World Bank Special\ud Programme of Research, Development and Research Training in Human\ud Reproduction (HRP), Department of Reproductive Health and Research,\ud World Health Organization, Geneva, Switzerland (project A65787), Merck\ud Sharp & Dohme Corp., a wholly owned subsidiary of Merck and Co., Inc.\ud (Kenilworth, NJ USA), through its Merck for Mothers program, and the United\ud States Agency for International Development (USAID). VB received support\ud for this project by the Health Resources and Services Administration (HRSA)\ud of the U.S. Department of Health and Human Services (HHS) under\ud T76MC00001 and entitled Center of Excellence in Maternal and Child Health\ud in Education, Science and Practice Training Grant. The views of the funding\ud bodies have not influenced the content of this protocol

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